Potassium Carbonate → HCID 22032947, compound

HRID 1373343Notes

Reaction equation

HRID 1373343 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=1)[CH:6]=[CH:5]2.[CH3:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:7]2[C:8]3[C:4](=[CH:3][C:2]([C:27]4[CH:26]=[CH:25][CH:24]=[C:23]([CH3:22])[CH:28]=4)=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)=[CH:13][CH:14]=1)([CH3:20])([CH3:21])[CH3:19]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27339503-Tolylboronic acid2×HCID 21964287HCID 21964287, compound2×

Product 1

HCID 22032947HCID 22032947, compoundYield 73%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of 5-bromo-1-(4-tert-butylbenzyl)-1H-indole (67.5 g, 197.2 mmol), 3-methylbenzeneboronic acid (27.6 g, 197.2 mmol), potassium carbonate (27.2 g, 493 mmol), palladium(II) acetate (0.338 g) and tetrabutylammonium bromide (63.5 g, 197.2 mmol) in 10% dioxane in water (degassed, 1.72 L) was stirred at 70° C. The reaction was monitored by TLC. 3-Methylbenzeneboronic acid (45.2 g, 394.4 mmol) was added in four portions every 10 hours, after which time 5-bromo-1-(4-tert-butylbenzyl)-1H-indole was no longer detected by TLC. The reaction was cooled to room temperature and the solvent was decanted. The dark gum-like oil was washed with water and extracted with petroleum ether (4×2 L). The combined petroleum ether extracts were washed with water and filtered. This filtrate was concentrated to a volume of about 1.5 L and allowed to crystallize. The solid was isolated by filtration and dried under vacuum at 60° C. for 10 hours to afford the title compound as a white solid (50.8 g, 73%), mp: 94–95° C. Mass spectrum (ESI, [M+H]+) m/z 354. 1HNMR (400 MHz, DMSO-d6): δ 7.79 (s, 1H), 7.53–7.51 (m, 2H), 7.45 (s, 1H), 7.41 (d, 1H, J=7.79 Hz), 7.37 (d, 2H, J=8.55 Hz), 7.32–7.28 (m, 3H), 7.14 (d, 2H, J=8.40 Hz), 7.09 (d, 1H, J=8.40 Hz), 6.51 (d, 1H, J=2.75 Hz), 5.38 (s, 2H), 2.36 (s, 3H), and 1.21 ppm (s, 9H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe solvent was decanted
  3. washThe dark gum-like oil was washed with water
  4. extractionextracted with petroleum ether (4×2 L)
  5. washThe combined petroleum ether extracts were washed with water
  6. filtrationfiltered
  7. concentrationThis filtrate was concentrated to a volume of about 1.5 L
  8. customto crystallize
  9. customThe solid was isolated by filtration
  10. customdried under vacuum at 60° C. for 10 hours

Sources & evidence

ORD record
ord-1d237d106e1742ce935cc78bf455436e
Source dataset
uspto-grants-2007_01
Patent number
US07160918B2

Reaction notes

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